Intronic (TTTGA)n insertion in SAMD12 also causes familial cortical myoclonic tremor with epilepsy.

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Citation: Movement Disorders. 34(10):1571-1576, 2019 10.PMID: 31483537Institution: MedStar Washington Hospital CenterDepartment: NeurologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Epilepsies, Myoclonic/ge [Genetics] | *Nerve Tissue Proteins/ge [Genetics] | *Tremor/ge [Genetics] | Adult | Asian Continental Ancestry Group | Epilepsies, Myoclonic/co [Complications] | Humans | Introns/ph [Physiology] | Male | Pedigree | Tremor/co [Complications]Year: 2019ISSN:
  • 0885-3185
Name of journal: Movement disorders : official journal of the Movement Disorder SocietyAbstract: BACKGROUND: Intronic (TTTCA)n insertions in the SAMD12, TNRC6A, and RAPGEF2 genes have been identified as causes of familial cortical myoclonic tremor with epilepsy.CONCLUSION: The targeted long-read sequencing helped us to elucidate the accurate structures of the (TTTGA)n and (TTTCA)n insertions. Our finding offers a novel possible cause for familial cortical myoclonic tremor with epilepsy and might shed light on the identification of genetic causes of this disease in pedigrees with no detected (TTTCA)n insertion in the reported causative genes. (c) 2019 International Parkinson and Movement Disorder Society. Copyright (c) 2019 International Parkinson and Movement Disorder Society.METHODS: Repeat-primed polymerase chain reaction, long-range polymerase chain reaction, and Sanger sequencing were performed to identify the existence of a novel (TTTGA)n insertion. Targeted long-read sequencing was performed to confirm the accurate structure of the (TTTGA)n insertion.OBJECTIVE: To identify the cause of familial cortical myoclonic tremor with epilepsy pedigrees without (TTTCA)n insertions in SAMD12, TNRC6A, and RAPGEF2.RESULTS: We identified a novel expanded intronic (TTTGA)n insertion at the same site as the previously reported (TTTCA)n insertion in SAMD12. This insertion cosegregated with familial cortical myoclonic tremor with epilepsy in 1 Chinese pedigree with no (TTTCA)n insertion. In the targeted long-read sequencing of 2 patients and 1 asymptomatic carrier in this pedigree, with 1 previously reported (TTTCA)n -insertion-carrying patient as a positive control, a respective total of 302, 159, 207, and 50 on-target subreads (predicated accuracy: >=90%) spanning the target repeat expansion region were generated. These sequencing data revealed the accurate repeat expansion structures as (TTTTA)114-123 (TTTGA)108-116 in the pedigree and (TTTTA)38 (TTTCA)479 in (TTTCA)n -insertion-carrying patient.All authors: Cen Z, Chen S, Chen X, Chen Y, Du X, Fu A, Hao W, Hu B, Jiang Z, Liu C, Liu Y, Luo W, Ouyang Z, Qiu X, Wang B, Wang H, Wang L, Xiao J, Xiao Y, Xie F, Yang D, Yang W, Yin H, Yu F, Yu X, Zhang B, Zhou Y, Zhu QOriginally published: Movement Disorders. 2019 Sep 04Fiscal year: FY2020Digital Object Identifier: Date added to catalog: 2019-10-10
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Journal Article MedStar Authors Catalog Article 31483537 Available 31483537

BACKGROUND: Intronic (TTTCA)n insertions in the SAMD12, TNRC6A, and RAPGEF2 genes have been identified as causes of familial cortical myoclonic tremor with epilepsy.

CONCLUSION: The targeted long-read sequencing helped us to elucidate the accurate structures of the (TTTGA)n and (TTTCA)n insertions. Our finding offers a novel possible cause for familial cortical myoclonic tremor with epilepsy and might shed light on the identification of genetic causes of this disease in pedigrees with no detected (TTTCA)n insertion in the reported causative genes. (c) 2019 International Parkinson and Movement Disorder Society. Copyright (c) 2019 International Parkinson and Movement Disorder Society.

METHODS: Repeat-primed polymerase chain reaction, long-range polymerase chain reaction, and Sanger sequencing were performed to identify the existence of a novel (TTTGA)n insertion. Targeted long-read sequencing was performed to confirm the accurate structure of the (TTTGA)n insertion.

OBJECTIVE: To identify the cause of familial cortical myoclonic tremor with epilepsy pedigrees without (TTTCA)n insertions in SAMD12, TNRC6A, and RAPGEF2.

RESULTS: We identified a novel expanded intronic (TTTGA)n insertion at the same site as the previously reported (TTTCA)n insertion in SAMD12. This insertion cosegregated with familial cortical myoclonic tremor with epilepsy in 1 Chinese pedigree with no (TTTCA)n insertion. In the targeted long-read sequencing of 2 patients and 1 asymptomatic carrier in this pedigree, with 1 previously reported (TTTCA)n -insertion-carrying patient as a positive control, a respective total of 302, 159, 207, and 50 on-target subreads (predicated accuracy: >=90%) spanning the target repeat expansion region were generated. These sequencing data revealed the accurate repeat expansion structures as (TTTTA)114-123 (TTTGA)108-116 in the pedigree and (TTTTA)38 (TTTCA)479 in (TTTCA)n -insertion-carrying patient.

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